The long term goal of the proposed research is to determine how T cells and lymphokines from T cells regulate the growth of B cells. Studies are planned in two major areas: (1) Function of B cell growth factors (BCGFs), (2) Role of T cells in activation of BCGF-responsive B cells. (1) Several aspects of the function of BCGFs will be addressed, including: (a) preparation and biochemical characterization of two distinct BCGFs (designated BCGFI [BSFpl] and BCGFII) for use in our own studies and in collaborative studies; (b) effects of these BCGFs on potential subpopulations of B cells defined by function, size, density, and cell surface markers; (c) effects on BCGFs on B cell growth cycle on kinetics of growth and on B cell response to other lymphokines; (d) attempts to develop in vitro clones of B cells maintained on, and responsive to, BCGFs. (2) Helper T cells will be compared to other agents in the activation of B cells for their response to BCGFs. (a) T cell hybridomas which activate B cells will be developed and compared with bulk populations of T cells for their ability to activate B cells; (b) B cell activation will be monitored by increase in B cell size, by exit of B cells from the resting G0 state, and by acquisition of responsiveness to BCGFI and BCGFII; (c) Anti-Ig and B cell mitogens lipopolysaccharide and dextran sulfate will be compared with T cells in these steps; (d) the role of lymphokines including IL1 and factors produced by the activating T cell hybridomas in B cell activation will be determined. In these studies, standard biochemical and molecular techniques will be used in combination with the in vitro culture of separated populations of normal and malignant B cells. The results of these studies will help us to understand the stages of the B cell life cycle and the regulation of those phases important in normal and malignant growth. These findings can help develop model systems to study further the mechanisms of oncogenesis which result in unregulated cell growth.